Aspects Of Multiple Sclerosis Research Articles

The Role of the Intestinal Microbiome in Multiple Sclerosis-Lessons to Be Learned from Hippocrates.

Based on recent advances in research of chronic inflammatory conditions, there is a growing body of evidence that suggests a close correlation between the microbiota of the gastrointestinal tract and the physiologic activity of the immune system. This raises the idea that disturbances of the GI ecosystem contribute to the unfolding of chronic diseases including neurodegenerative pathologies. Here, we overview our current understanding on the putative interaction between the gut microbiota and the immune system from the aspect of multiple sclerosis, one of the autoimmune conditions accompanied by severe chronic neuroinflammation that affects millions of people worldwide.

Multiple sclerosis: new insights into molecular pathogenesis and novel platforms for disease treatment.

Multiple sclerosis (MS), a chronic inflammatory disorder, affects the central nervous system via myelin degradation. The cause of MS is not fully known, but during recent years, our knowledge has deepened significantly regarding the different aspects of MS, including etiology, molecular pathophysiology, diagnosis and therapeutic options. Myelin basic protein (MBP) is the main myelin protein that accounts for maintaining the stability of the myelin sheath. Recent evidence has revealed that MBP citrullination or deamination, which is catalyzed by Ca2+ dependent peptidyl arginine deiminase (PAD) enzyme leads to the reduction of positive charge, and subsequently proteolytic cleavage of MBP. The overexpression of PAD2 in the brains of MS patients plays an essential role in new epitope formation and progression of the autoimmune disorder. Some drugs have recently entered phase III clinical trials with promising efficacy and will probably obtain approval in the near future. As different therapeutic platforms develop, finding an optimal treatment for each individual patient will be more challenging. This review provides a comprehensive insight into MS with a focus on its pathogenesis and recent advances in diagnostic methods and its present and upcoming treatment modalities. MS therapy alters quickly as research findings and therapeutic options surrounding MS expand. McDonald's guidelines have created different criteria for MS diagnosis. In recent years, ever-growing interest in the development of PAD inhibitors has led to the generation of many reversible and irreversible PAD inhibitors against the disease with satisfactory therapeutic outcomes.

Assisted Reproductive Technology and Disease Management in Infertile Women with Multiple Sclerosis.

Multiple sclerosis (MS) predominantly affects women of fertile age. Various aspects of MS could impact on fertility, such as sexual dysfunction, endocrine alterations, autoimmune imbalances, and disease-modifying therapies (DMTs). The proportion of women with MS (wMS) requesting infertility management and assisted reproductive technology (ART) is increasing over time. In this review, we report on data regarding ART in wMS and address safety issues. We also discuss the clinical aspects to consider when planning a course of treatment for infertility, and provide updated recommendations to guide neurologists in the management of wMS undergoing ART, with the goal of reducing the risk of disease activation after this procedure. According to most studies, there is an increase in relapse rate and magnetic resonance imaging activity after ART. Therefore, to reduce the risk of relapse, ART should be considered in wMS with stable disease. In wMS, especially those with high disease activity, fertility issues should be discussed early as the choice of DMT, and fertility preservation strategies might be proposed in selected cases to ensure both disease control and a safe pregnancy. For patients with stable disease taking DMTs compatible with pregnancy, treatment should not be interrupted before ART. If the ongoing therapy is contraindicated in pregnancy, then it should be switched to a compatible therapy. Prior to beginning fertility treatments in wMS, it would be reasonable to assess vitamin D serum levels, thyroid function and its antibody serum levels; start folic acid supplementation; and ensure smoking and alcohol cessation, adequate sleep, and food hygiene. Cervico-vaginal swabs for Ureaplasma urealyticum, Mycoplasma hominis, and Chlamydia trachomatis, as well as serology for viral hepatitis, HIV, syphilis, and cytomegalovirus, should be performed. Steroids could be administered under specific indications. Although the available data do not clearly show a definite raised relapse risk associated with a specific ART protocol, it seems reasonably safe to prefer the use of gonadotropin-releasing hormone (GnRH) antagonists for ovarian stimulation. Close clinical and radiological monitoring is reasonably recommended, particularly after hormonal stimulation and in case of pregnancy failure.

Iranian specialists' approach to surgery in patients with multiple sclerosis.

Background: Data on perioperative risk stratification in patients with multiple sclerosis (MS) are limited. In this regard, the present study was conducted to investigate Iranian specialists' approach to surgical counseling for patients with MS (PwMS). Methods: 21 MS specialists were asked about 11 case scenarios with different MS disease statuses, disease-modifying therapies (DMTs), and urgency of the operation. The reasons for refusing surgery or factors that have to be considered before surgery were studied. Results: Overall, Fleiss Kappa was estimated to be 0.091 [95% confidence interval (CI): 0.090-0.093, P < 0.001] indicating a very poor level of agreement among responders. Conclusion: PwMS face surgery for various reasons. Risk assessment of surgery, the effect of various drugs such as anesthetics and DMT on patients, as well as many other aspects of MS are issues challenging the practitioners. Clarifying the various dimensions of these issues requires further research.

What's your cup of tea? The role of herbal compounds in the management of multiple sclerosis.

Multiple Sclerosis (MS) is a chronic, inflammatory, neurodegenerative disease that is characterized by a complex etiology. Efforts towards the management of MS have long been directed towards symptomatic relief, as well as the use of immune-modulatory, disease modifying therapies; however, inconsistent treatment responses still prevail, increasing the risk for disease progression. While a great deal of research attempted to unravel the complexity of treatment responses in light of epigenetic variability, parallel efforts in the direction of alternative medicine may be as paramount. Herbal compounds have long been regarded as safe and versatile options for aiding in various disorders, including neurodegenerative conditions like MS. Numerous studies have taken interest in a myriad of herbal plants for their potential benefit in alleviating some of the most common MS symptoms such as spasticity and fatigue, delaying the progression of the disease, as well as influencing the overall quality of life for MS patients. This review aims to provide a comprehensive overview of recent clinical studies examining the effects of various herbal plants on different aspects of MS, in an attempt to shed light on an important tool for aiding in the management of this complex and multifactorial disease.

The potential roles of amino acids and their major derivatives in the management of multiple sclerosis.

Recently, we reviewed the important role of carbohydrates and lipids metabolism in different clinical aspects of multiple sclerosis (MS) disease. In the current paper, we aimed to review the contribution of amino acids and their major derivatives to different clinical outcomes of the disease, including etiology, pathogenesis, diagnosis, prognosis, and treatment. In this line, Thr (threonine), Phe (phenylalanine), Glu (glutamate), Trp (tryptophan), and Sero (serotonin) are the main examples of biomolecules that have been suggested for MS therapy. It has been concluded that different amino acids and their derivatives might be considered prominent tools for the clinical management of MS disease.

Twin study probes non-heritable immune aspects of multiple sclerosis.

Twin study probes non-heritable immune aspects of multiple sclerosis.

Knowledge towards Multiple Sclerosis among Family Medicine Residents in Makkah City, Saudi Arabia

Background: Early identification and management of multiple sclerosis (MS) related symptoms and comorbidities by physicians can lead to better outcomes, improved quality of life, and reduced disease activity. Objectives: To evaluate the knowledge towards multiple sclerosis among family medicine residents. Methods: A cross-sectional study was carried out among a representative sample Family Medicine residents enrolled in the joint program of Family Medicine in Makkah, 2020. Self-administered questionnaire was used for data collection. It includes two main parts; personal characteristics of the participants and assessment of their knowledge about different aspects of MS through 30 multiple choice questions. Results: A total of 116 Family Medicine residents participated in this study. Most of them (70.7%) aged between 26 and 30 years. Equally distributed regarding gender. History of attending conference about multiple sclerosis or neurological disorder was reported by 13.8% of the participants. Overall, 56.9% of family Medicine residents expressed good level of knowledge regarding MS. Female resident physicians were more knowledgeable about MS than males (69% vs. 44.8%), p=0.009. Majority (83.3%) of PGY4 resident physicians compared to only 47.2% and 47.4% of PGY3 and PGY2 resident physicians, respectively had good level of knowledge, p=0.040. Conclusion: A considerable percentage of family Medicine residents in Makkah city, Saudi Arabia expressed poor level of knowledge regarding all aspects of multiple sclerosis; particularly males. The highest level of knowledge was observed regarding treatment of MS, followed by complications while the lowest level was reported regarding symptoms.

Managing respiratory dysfunction in people with multiple sclerosis

There are many aspects of multiple sclerosis that require careful monitoring; among them is respiratory support. Jody Barber elaborates on what can be done to optimise respiratory health for patients.

Asymptomatic Herpes Simplex Virus Type 1 Infection Causes an Earlier Onset and More Severe Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is an increasingly prevalent progressive autoimmune and debilitating chronic disease that involves the detrimental recognition of central nervous system (CNS) antigens by the immune system. Although significant progress has been made in the last decades on the biology of MS and the identification of novel therapies to treat its symptoms, the etiology of this disease remains unknown. However, recent studies have suggested that viral infections may contribute to disease onset. Interestingly, a potential association between herpes simplex virus type 1 (HSV-1) infection and MS has been reported, yet a direct relationship among both has not been conclusively demonstrated. Experimental autoimmune encephalomyelitis (EAE) recapitulates several aspects of MS in humans and is widely used to study this disease. Here, we evaluated the effect of asymptomatic brain infection by HSV-1 on the onset and severity of EAE in C57BL/6 mice. We also evaluated the effect of infection with an HSV-1-mutant that is attenuated in neurovirulence and does not cause encephalitis. Importantly, we observed more severe EAE in mice previously infected either, with the wild-type (WT) or the mutant HSV-1, as compared to uninfected control mice. Also, earlier EAE onset was seen after WT virus inoculation. These findings support the notion that a previous exposure to HSV-1 can accelerate and enhance EAE, which suggests a potential contribution of asymptomatic HSV-1 to the onset and severity of MS.

Calming the (Cytokine) Storm: Dimethyl Fumarate as a Therapeutic Candidate for COVID-19.

COVID-19 has rapidly spread worldwide and incidences of hospitalisation from respiratory distress are significant. While a vaccine is in the pipeline, there is urgency for therapeutic options to address the immune dysregulation, hyperinflammation and oxidative stress that can lead to death. Given the shared pathogenesis of severe cases of COVID-19 with aspects of multiple sclerosis and psoriasis, we propose dimethyl fumarate as a viable treatment option. Currently approved for multiple sclerosis and psoriasis, dimethyl fumarate is an immunomodulatory, anti-inflammatory and anti-oxidative drug that could be rapidly implemented into the clinic to calm the cytokine storm which drives severe COVID-19.

Familial aggregation of multiple sclerosis: Results from the national registry of the disease in Saudi Arabia.

BackgroundMultiple Sclerosis (MS) is a chronic CNS inflammatory disease commonly affecting young adults. Both genetics and environmental factors have been reported to have a role in pathophysiology of the disease.ObjectiveThis article aims to report familial nature and aspects of MS in Saudi Arabia.MethodThe study utilized data collected by the National Saudi MS Registry between 2015 and 2018; especially data relevant to the familial history of MS. SPSS 22 was used for all analysis and reporting. Statistical significance was set at p-value < 0.05.ResultsThe registry included 20 hospitals and a total of 2516 patients from the different regions of Saudi Arabia with median age 32.00 (Range: 11–63) and 66.5% being female. About 12.8% of all registered patients reported a family history of MS (95%CI: 11.2-13.9). Reported parental consanguinity was significantly higher among patients with family history (FMS) (56.3%) compared to non-FMS patients (27.9%). 42.53% of FMS patients reported having siblings affected with MS (95%CI: 37.01–48.21), with more female siblings affected than males (63.4% vs 36.6% respectively).ConclusionOur Findings suggested that FMS was less prevalent than what was reported previously; however, parental consanguinity was significantly more prevalent among FMS patients than non-FMS. Our findings were in line with those reported in recent studies in the region, but lower than those reported by western countries indicating that increasing prevalence of MS in Saudi Arabia could be multifactorial and other environmental factors should be considered for understanding this recent rise in the prevalence of MS in Saudi Arabia.

Recent advances in network medicine: From disease mechanisms to new treatment strategies

Conventional reductionist approaches have guided most of our understanding in disease diagnostic and treatment. However, most diseases are not consequence of perturbations in a single protein or metabolite, but rather of the effect that these perturbations have in their cellular context. The emerging field of network medicine offers a set of tools to explore molecular networks and to retrieve insights about mechanisms of different diseases. The study of the protein interactome, the map of physical interactions among human proteins, revealed that disease proteins tend to interact with each other, linking diseases to well-defined interactome neighborhoods. These disease-associated neighborhoods have been defined as disease modules, and they can uncover the biological significance of genes identified by genetic studies, reveal molecular mechanisms that connect different phenotypes, and help identify new pharmacological strategies for disease treatment. Therefore, network medicine offers a framework in which the complexity of different aspects of multiple sclerosis can be explored in an integrative fashion, which can ultimately provide insights about disease mechanisms and treatment.

Central nervous system targeted autoimmunity causes regional atrophy: a 9.4T MRI study of the EAE mouse model of Multiple Sclerosis

Atrophy has become a clinically relevant marker of progressive neurodegeneration in multiple sclerosis (MS). To better understand atrophy, mouse models that feature atrophy along with other aspects of MS are needed. The experimental autoimmune encephalomyelitis (EAE) mouse model of MS was used to determine the extent of atrophy in a model of inflammation-associated central nervous system pathology. High-resolution magnetic resonance imaging (MRI) and atlas-based volumetric analysis were performed to measure brain regional volumes in EAE mice. EAE brains were larger at peak clinical disease (days 14–16) compared to controls, with affected regions including the cerebellum, hippocampus, and corpus callosum. Following peak clinical disease, EAE mice exhibited significant loss of volume at chronic long-term disease duration (day 66+). Atrophy was identified in both white and grey matter regions including the cerebral cortex, cerebellum, hippocampus, corpus callosum, basal forebrain, midbrain, optic tract, and colliculus. Histological analysis of the atrophied cortex, cerebellum, and hippocampus showed demyelination, and axonal/neuronal loss. We hypothesize this atrophy could be a result of inflammatory associated neurodegenerative processes, which may also be involved in MS. Using MRI and atlas-based volumetrics, EAE has the potential to be a test bed for treatments aimed at reducing progressive neurological deterioration in MS.

Immune and autonomic nervous system interactions in multiple sclerosis: clinical implications.

Multiple sclerosis is characterized by a wide spectrum of clinical manifestations, among which dysfunction of the autonomic nervous system represents an important cause of multiple sclerosis-related disability. The aim of this review is to provide an overview of autonomic dysfunction in people with multiple sclerosis, and to discuss the interactions between the immune and autonomic nervous systems and the effects of these interactions on various aspects of multiple sclerosis. Autonomic dysfunction in people with multiple sclerosis can be demonstrated clinically and on a molecular level. Clinically, it can be demonstrated by measuring autonomic symptoms with the Composite Autonomic Symptom Score (COMPASS-31), and neurophysiologically, with different autonomic nervous system tests. Both symptomatic and objectively determined autonomic dysfunction can be associated with increased risk of multiple sclerosis disease activity. Further supporting these clinical observations are molecular changes in immune cells. Changes in the sympathetic autonomic system, such as different expression of dopaminergic and adrenergic receptors on immune cells, or modulation of the cholinergic anti-inflammatory pathway over different subunits of the nicotinic acetylcholine receptor in the peripheral immune system, may mediate different effects on multiple sclerosis disease activity.

Clinical Aspects of Multiple Sclerosis: An Observational Study From The Sheikh Khalifa Medical City in Abu Dhabi

Clinical Aspects of Multiple Sclerosis: An Observational Study From The Sheikh Khalifa Medical City in Abu Dhabi

Break-out session highlights.

A popular feature of the Multiple Sclerosis Experts Summit is interactive break-out sessions to discuss various aspects of multiple sclerosis (MS), including MS spasticity and general management of MS patients. The format encourages participation and active discussion, thus providing attendees with the opportunity to exchange their experiences of the day-to-day management of MS in clinical practice. Following feedback provided by each session leader, key messages are summarized and presented in a plenary session by the Summit chair. Topics covered in this year's country break-out sessions included: triggering factors for MS; decision-making in MS and the importance of patients' risk perception; assessment and management of MS spasticity.

Processo epigenéticos envolvidos na fisiopatologia da esclerose múltipla com ênfase na função dos miRNAs

A esclerose múltipla (EM) é uma doença neurodegenerativa autoimune do sistema nervoso central (SNC). A fisiopatologia caracteriza-se por intensa atividade inflamatória e envolvimento de células do sistema imune (TCD4+, TCD8+ e linfócitos B); células da glia e uma desregulação da permeabilidade da barreira hematoencefálica (BHE). Atualmente a sua etiologia permanece desconhecida e acredita-se que os fatores ambientais e uma predisposição genética sejam os responsáveis pela autoimunidade. Discrepâncias em padrões de herança genética da doença, prevalência de gênero e baixa taxa de concordância entre gêmeos homozigotos sugerem a atuação de processos epigenéticos na esclerose múltipla. Os processos epigenéticos são responsáveis pela expressão gênica sem ocasionar uma alteração no código genético e são altamente sensíveis a variações do meio ambiente. Ademais são preservados entre divisões celulares e interferem em diferentes processos biológicos; porém podem ser revertidos. Os três processos mais bem estudados são a metilação de DNA, a acetilação de histonas e o silenciamento gênico por miRNAs. Os miRNAs especificamente vem sendo alvo de pesquisas uma vez que regulam um terço da expressão gênica em mamíferos. Esses pequenos segmentos de RNA de aproximadamente 22 nucleotídeos tem elucidado diversos aspectos da EM e parecem interagir e regular células do sistema imune e do SNC; podendo vir a se tornar valiosos biomarcadores para a mesma.

High Dimensional Cytometry of Central Nervous System Leukocytes During Neuroinflammation.

Autoimmune diseases like multiple sclerosis (MS) develop from the activation and complex interactions of a wide network of immune cells, which penetrate the central nervous system (CNS) and cause tissue damage and neurological deficits. Experimental autoimmune encephalomyelitis (EAE) is a model used to study various aspects of MS, including the infiltration of autoaggressive T cells and pathogenic, inflammatory myeloid cells into the CNS. Various signature landscapes of immune cell infiltrates have proven useful in shedding light on the causes of specific EAE symptoms in transgenic mice. However, single cell analysis of these infiltrates has thus far been limited in conventional fluorescent flow cytometry methods by 14-16 parameter staining panels. With the advent of mass cytometry and metal-tagged antibodies, a staining panel of 35-45 parameters is now possible. With the aid of dimensionality reducing and clustering algorithms to visualize and analyze this high dimensional data, this allows for a more comprehensive picture of the different cell populations in an inflamed CNS, at a single cell resolution level. Here, we describe the induction of active EAE in C56BL/6 mice and, in particular, the staining of microglia and CNS invading immune cells for mass cytometry with subsequent data visualization and analysis.

New Discernment of Pathophysiological Aspects of Multiple Sclerosis Based On Mono Amino Oxidase (MAO) and Ion Channel Receptor 5HT3RA as Activator of T-Cells

Background: Multiple sclerosis (MS) is a chronic, inflammatory and autoimmune disease of central nervous system. MS affects nearly 2.5 million people in the world and is twice more common in women than men. Autoimmune T-cells target the myelin sheath in central nervous system, causing inflammation, demyelination and eventual destruction of neurons. We examined changing expression of serotonin receptor (5-HT3RA) as well as monoamine oxidase (MAO-A) genes in peripheral blood mononuclear cells in MS patients. Materials and methods: In this study, peripheral blood mononuclear cells (PBMC) were first isolated from 30 healthy controls and 30 volunteers with MS using Ficoll-hypaque. Total RNA was extracted and cDNA was synthesized. In this process, mRNA concentration of 5-HT3RA and MAO-A as target genes as well as β-actin as reference gene was compared in PBMC of healthy subjects and patients using Real-time PCR. Results: After statistical analysis of resulting data, a significant increase was observed in the expression of 5-HT3RA receptor gene as well as MAO-A gene in PBMC of patients with multiple sclerosis (P=0.001). Conclusion: According to previous studies on the association between serotonin level with MS importance of 5-HT3RA serotonin receptor in the function of this neurotransmitter as well as T-cell activation along with significant increase in the expression of 5-HT3RA receptor in MS patients, it can be concluded that overexpression of this receptor has a significant correlation with MS progress. On the other hand, considering the fact that monoamine oxidase is a key enzyme responsible for oxidation of serotonin in the nervous system, perhaps the body is not capable of maintaining normal level of this enzyme in MS patients. Therefore, considerable increase in MAO level may be responsible for reduced level of serotonin in MS patients, which is a likely reason for depression in these patients.